This is a really solid, useful piece of content.
The obvious use is for portraying Skullport, and it is quite excellent at that. The writing really makes it feel like an interesting (if not pleasant) place to visit and set adventures in. There are tons of fascinating details and dangling adventure hooks peppered throughout the book, and taken as a whole, they provide enough material where I feel like I could run a mini-campaign in just Skullport itself and its surrounding environs. As one would expect to find in such a place, Skullport is littered with ongoing injustices and cruelties, and a sufficiently-motivated (and smart!) good or empathetic party could find a lot to keep them busy. The author mentions in the foreward that she could easily write a novel set in Skullport, and reading over the various NPC and location entries, you can get a sense as to what such a novel might look like. There is very little wasted text in the book, and almost everything points to something fun you could throw at a PC group.
The content warnings definitely belong there - the book goes to some heavy and dark places, but it is handles with taste and care. The author also explicitly advises the use of safety tools, which is something I wish I saw more often in general. Also, despite the fact that the material is clearly for a very specific part of the Forgotten Realms, I could (and likely will) adapt a lot of this material to a homebrew setting. Many of the shops and even some of the factions can be lifted neatly out of skullport and dropped into any pirate haven, fantasy slum or similarly-rough-and-desperate type of area. Even fairly minor locations have interesting bits of lore (the way the butcher/corpse trader refrigerates his wares was an especially clever example).
There's also a significant amount of quality design work in here. It's nice to have some capture weapons for 5e, and the author has brought back a number of interesting mechanical bits from previous editions such as the delightfully creepy bonefiddle spell and the Elven Courtblade weapon. The five new subclasses and the new background in here will all have lots to do in Skullport, but they're also highly-portable to other worlds with minor (or no) tweaks and well-realized from a mechanical point of view.
There are a number of useful new rules for drugs and psychological trauma in here too - the new Haunted condition in particular is an elegant and flavorful piece of design, and the drugs are designed in such a way that they'll be tempting enough to players that they might be willing to risk addiction for the edge they give. There's also a section at the front about interesting new resources and a couple of fun surprises of mechanical goodness sprinkled into the locatation entries. And that doesn't even get into the new magic items, which are also excellent. (I need to remember that Bracer of Flying Daggers for my next rogue PC!)
All in all, this is a really solid, well-written, interesting and useful piece of content that I am very happy to have in my library.
[5 of 5 Stars!]